海马Na+-K+-2C1-协同转运蛋白对七氟醚致新生大鼠神经行为损伤的影响

Jia Li, Jianwei Wang, Meng Wang, Bo Ren, Chang-sheng Li, Xihua Lu, C. Miao
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摘要

目的探讨海马Na+-K+-2C1-协同转运蛋白(NKCC1)对七氟醚诱导的新生大鼠神经行为损伤的影响。方法36只6日龄雄性Sprague-Dawley大鼠按随机数表法分为三组(n=12):对照组(C组)、七氟醚组(S组)和七氟醚+布美他尼组(SB组)。C组吸入30%氧气6h,S组和SB组吸入2.1%七氟醚+30%氧气6h。SB组在七氟醚吸入前15min腹膜内注射布美他奈(1.82mg/kg)。然后,4周后,进行升高+迷宫和脉冲前抑制(PPI)测试。行为测试一周后,海马体被采集。采用实时定量PCR和蛋白质印迹法检测NKCC1mRNA和蛋白水平。结果在升高加迷宫试验中,三组的总运动距离无显著差异(P<0.05)。与C组相比,S组缩短了双臂停留时间,PP3和PP6的PPI%降低(P<0.05),海马NKCC1mRNA和蛋白质含量增加(P<0.05),SB组大鼠张开臂时间延长,PP3和PP6对应的PPI%增加,海马NKCC1mRNA和蛋白质含量下降(P<0.05)。结论七氟醚可能引起新生大鼠神经行为损伤,可能与NKCC1有关。关键词:七氟烷;Na+-K+-2C1-协同转运蛋白;海马;神经行为学;新生大鼠
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Effects of hippocampal Na+-K+-2C1- cotransporter on sevoflurane-induced neurobehavioral impairments in neonatal rats
Objective To discuss the effects of hippocampal Na+-K+ -2C1- cotransporter (NKCC1) on sevoflurane-induced neurobehavioral impairments in neonatal rats. Methods Thirty six 6-day-old male Sprague-Dawley rats were divided into three groups (n=12), according to the random number table method: a control group (group C), a sevoflurane group (group S), and a sevoflurane + bumetanide group (group SB). Group C inhaled 30% oxygen for 6 h, while groups S and SB inhaled 2.1% sevoflurane+30% oxygen for 6 h. Group SB was intraperitoneally injected with bumetanide (1.82 mg/kg) 15 min before sevoflurane inhalation. Then, 4 weeks later, the elevated plus maze and prepulse inhibition (PPI) tests were performed. One week after behavior tests, the hippocampus was harvested. Quantitative real time PCR and Western blot were used to detect the levels of NKCC1 mRNA and protein. Results In the elevated plus maze test, no significant difference was observed in total movement distance among the three groups (P<0.05). Compared with group C, group S spent shortened time of stay in the open arms, presented decreased PPI% corresponding to PP3 and PP6 (P<0.05), and produced increased amounts of hippocampal NKCC1 mRNA and protein (P<0.05). Compared with group S, group SB presented extended time in the open arms, increased PPI% corresponding to PP3 and PP6, and declined amounts of hippocampal NKCC1 mRNA and protein (P<0.05). Conclusions Sevoflurane may cause neurobehavioral damages in neonatal rats, which may be associated with NKCC1. Key words: Sevoflurane; Na+-K+ -2C1- cotransporter; Hippocampus; Neuroethology; Neonatal rats
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